Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failure

A hallmark of overt congestive heart failure (CHF) is attenuated cGMP production by endogenous atrial natriuretic peptide (ANP) with renal resistance to ANP. ANP and brain natriuretic peptides (BNP) are of myocardial origin, whereas urodilatin (Uro) is thought to be derived from kidney. All three peptides are agonists to the natriuretic peptide-A receptor. Our objective was to compare the cardiorenal and humoral actions of ANP, BNP, and Uro in experimental overt CHF. We determined cardiorenal and humoral actions of 90 min of intravenous equimolar infusion of ANP, BNP, and Uro (2 and 10 pmol·kg −1 ·min −1 ) in three separate groups of anesthetized dogs with rapid ventricular pacing-induced overt CHF (240 beats/min for 10 days). BNP resulted in increases in urinary sodium excretion (U Na V) (2.2 ± 0.7 to 164 ± 76 μeq/min, P < 0.05) and glomerular filtration rate (GFR) (27 ± 4 to 52 ± 11 ml/min, P < 0.05) that were greater than those with Uro ( P < 0.05), whereas ANP did not result in increases in U Na V or GFR. Increases in plasma cGMP (25 ± 2 to 38 ± 2 pmol/ml, P < 0.05) and urinary cGMP excretion with BNP (1,618 ± 151 to 6,124 ± 995 pmol/min, P < 0.05) were similar to those with Uro; however, there was no change with ANP. Cardiac filling pressures were reduced in all three groups. These studies also support the conclusion that in experimental overt CHF, renal resistance to natriuretic peptides in increasing rank order is BNP < Uro < ANP.